Lymphokines are substances produced by lymphocytes and monocytes that have important functions in lymphoid cell interactions and regulation. Recently, we have observed that supernatants of mixed lymphocyte reactions can stimulate fibroblast proliferation in vitro. We demonstrated that interleukin-1 (IL-1), a lymphokine known to be produced by monocytes, was responsible for this effect. This was shown by comparison of thermocyte proliferative activation, the classical assay for IL-1, and fibroblast proliferative activation. The substances mediating these activities migrated together on gel filtration on sepacryl S-200, phenylsepharose chromatography, HPLC size exclusion chromatography and isselectric focusing. Adding silica to purified monocyte mono-layers stimulated the production of IL-l. The fibrosis observed in the lungs after silica inhalation may be explained by these observations. The general conclusion reached is that lymphokines and in particular IL-l may have important effects on non-lymphoid tissues.